title: Trafficking and homing of systemically administered stem cells: the need for appropriate analysis tools of radionuclide images.
abstract: OBJECTIVE
  Despite its enormous relevance, homing of hematopoietic stem cells (SCs) remains relatively uncertain due to the limitations of measuring small number of systemically administered cells in the different organs. Despite its high sensitivity, radionuclide detection has been relatively underutilized to this purpose since it cannot differentiate hematopietic SCs recruited by target tissues from those circulating in the blood pool. Our study aims to verify the potential of tracer kinetic approaches in estimating the recruitment of labeled SCs after their systemic administration.
  
  
  METHODS
  Twenty-four Lewis rats underwent administration of 2 millions cells labeled with 37 MBq of 99mTc-exametazime. Animals were divided into 2 groups according to administered cells: hematopoietic SCs or cells obtained from a line of rat hepatoma. Cell injection was performed during a planar dynamic acquisition. Regions of interest were positioned to plot time activity curves on heart, lungs, liver and spleen. Blood cell clearance was evaluated according to common stochastic analysis approach. Either fraction of dose in each organ at the end of the experiment or computing the slope of regression line provided by Patlak or Logan graphical approach estimated cell recruitment. At the end of the study, animals were sacrificed and the number of cells retained in the same organs was estimated by in vitro counting.
  
  
  RESULTS
  Cell number, documented by the dose fraction retained in each organ at imaging was consistently higher with respect to the "gold standard" in vitro counting in all experiments. An inverse correlation was observed between degree of overestimation and blood clearance of labeled cells (r=-0.56, P<0.05). Logan plot analysis consistently provided identifiable lines, whose slope values closely agreed with the "in vitro" estimation of hepatic and splenic cell recruitment.
  
  
  CONCLUSIONS
  The simple evaluation of organ radioactivity concentration does not provide reliable estimates of local recruitment of systemically administered cells. Yet, the combined analysis of temporal trends of tracer (cell) tissue accumulation and blood clearance can provide quantitative estimations of cell homing in the different organs.
authors.affiliation: Department of Internal Medicine, University of Genoa, Genoa, Italy. sambuceti@unige.it
authors.forename: G
authors.initials: G
authors.lastname: Sambuceti
authors.forename: M
authors.initials: M
authors.lastname: Massollo
authors.forename: C
authors.initials: C
authors.lastname: Marini
authors.forename: M
authors.initials: M
authors.lastname: Podestà
authors.forename: C
authors.initials: C
authors.lastname: Cassanelli
authors.forename: S
authors.initials: S
authors.lastname: Morbelli
authors.forename: F
authors.initials: F
authors.lastname: Fiz
authors.forename: A
authors.initials: A
authors.lastname: Buschiazzo
authors.forename: S
authors.initials: S
authors.lastname: Capitanio
authors.forename: C
authors.initials: C
authors.lastname: Augeri
authors.forename: G
authors.initials: G
authors.lastname: Curti
authors.forename: M
authors.initials: M
authors.lastname: Piana
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000818:Animals; D002074:Butanones; D058948:Cell Tracking / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000000981:diagnostic imaging*; D008297:Male; D014411:Neoplastic Stem Cells / Q000000981:diagnostic imaging* / Q000637:transplantation*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013667:Technetium
chemical_list: D002074:Butanones; D019275:Radiopharmaceuticals; D013667:Technetium; C078058:exametazime